Differences in Genomic Alterations and Accumulations of Heavy Metals Between Advanced Non-small Cell Lung Cancer Patients with and without Bone Metastasis.

Purpose: Bone metastasis (BoM) has been closely associated with increased morbidity and poor survival outcomes in patients with non-small cell lung cancer (NSCLC). Given its significant implications, this study aimed to systematically compare the biological characteristics between advanced NSCLC patients with and without BoM. Methods: In this study, the genomic alterations from the tumor tissue DNA of 42 advanced NSCLC patients without BoM and 67 patients with BoM and were analyzed by a next-generation sequencing (NGS) panel. The serum concentrations of 18 heavy metals were detected by inductively coupled plasma emission spectrometry (ICP-MS). Results: A total of 157 somatic mutations across 18 mutated genes and 105 somatic mutations spanning 16 mutant genes were identified in 61 out of 67 (91.05%) patients with BoM and 37 of 42 (88.10%) patients without BoM, respectively. Among these mutated genes, NTRK1, FGFR1, ERBB4, NTRK3, and FGFR2 stood out exclusively in patients with BoM, whereas BRAF, GNAS, and AKT1 manifested solely in those without BoM. Moreover, both co-occurring sets of genes and mutually exclusive sets of genes in patients with BoM were different from those in patients without BoM. In addition, the serum concentrations of Cu and Sr in patients with BoM were significantly higher than in patients without BoM. One of our aims was to explore how these heavy metals associated with BoM interacted with other heavy metals, and significant positive correlations were observed between Cu and Co, between Cu and Cr, between Sr and Ba, and between Sr and Ni in patients with BoM. Given the significant impacts of molecular characteristics on patients' prognosis, we also observed a noteworthy negative correlation between EGFR mutations and Co, alongside a significant positive correlation between TP53 mutations and Cd. Conclusions: The genomic alterations, somatic interactions, key signaling pathways, functional biological information, and accumulations of serum heavy metals were markedly different between advanced NSCLC patients with and without BoM, and certain heavy metals (e.g., Cu, Sr) might have potentials to identify high-risk patients with BoM.

Campylotropis xinfeniae (Fabaceae, Papilionoideae), a new species from Yunnan, China, based on morphological and molecular evidence.

Campylotropis xinfeniae, a new species from the dry-hot valley of the Jinsha River in the Yunnan province, China, is described and illustrated. It is morphologically similar to C. wilsonii and C. brevifolia in having glabrescent old branches, absent stipels, 3-foliolate leaves, and adaxially puberulent leaflets, while it differs from the latter two in having often paniculate inflorescences, obviously white standard, not incurved sickle keel, larger narrowly oblique legumes, and longer legume beak. The complete chloroplast genome of this new species is 149,073 bp in length and exhibits a typical quadripartite structure. Phylogenetic analyses based on the complete chloroplast genome also supported C. xinfeniae as a new species located at the basal distinct clade of the genus Campylotropis, clearly separated from the remaining members of the genus and its allied genera. A conservation assessment of data deficient (DD) is recommended for the new species without extensive exploring of similar habitats according to the IUCN Categories and Criteria.

Bilateral Multiple Fractures Obstruct Quantitation of 99m Tc-Pyrophosphate Imaging for Cardiac Amyloidosis.

ABSTRACT: A 57-year-old woman who had persistent symptoms of transthyretin cardiac amyloidosis underwent 99m Tc-pyrophosphate ( 99m Tc-PYP) scintigraphy. The 99m Tc-PYP planar and SPECT/CT fusion image showed diffuse myocardial uptake and multiple fractures of the sternum and ribs. These fractures interfered with semiquantitative scores of 99m Tc-PYP uptake, leading to false positive in 99m Tc-PYP imaging.

S vacancies-introduced chalcopyrite switch radical to non-radical pathways via peroxymonosulfate activation: Vital roles of S vacancies.

Regulation of peroxymonosulfate (PMS) activation from radical to non-radical pathways is an emerging focus of advanced oxidation processes (AOPs) due to its superiority of anti-interference to complex wastewater. However, the detailed correlation mechanism between the defect structure of the catalyst and the regulation of radicals/non-radicals remains unclear. Herein, natural chalcopyrite (CuFeS2) with different levels of S vacancies created by a simple NaBH4 reduction process was employed to explore the above-mentioned underlying mechanism for constructing high efficiency and low cost of catalyst towards AOPs. With the assistance of simulated solar light, S-deficient chalcopyrite (Sv-NCP) exhibited prominent performance for PMS activation. More interestingly, the different degrees of S vacancies regulated the active species from radicals to non-radical 1O2, thus showing excellent purification of complex wastewater as well as actual pharmaceutical wastewater. Mechanistic analysis reveals that PMS tends to loss electrons on S vacancies sites and is dissociated into 1O2 rather than ·OH/SO4·- due to electron deficiency. Meanwhile, the improved adsorption performance makes the degradation sites of pollutants change from solution to surface. Most importantly, Sv-NCP presented excellent detoxication for antibiotic wastewater due to the high selectivity of 1O2. This work provides novel insights into the regulation of active species in Fenton-like reactions via defect engineering for high efficiency of pollutant degradation.

Realization of white-light-emitting diodes from a high-brightness zirconium-based metal-organic gel driven by the AIE effect.

Developing luminescent materials with suitable correlated color temperature (CCT) and sufficient color-rendering index (CRI) is a challenging problem in the field of commercialized warm white LED lighting. Herein, a novel metal-organic gel (MOG) material named YTU-G-1(SE) was synthesized, consisting of zirconium metal coordinated with 1,1,2,2-tetrakis(4-carboxyphenyl) ethylene. YTU-G-1(SE) exhibits strong fluorescent properties with an aggregation-induced emission (AIE) effect, emitting yellow-green fluorescence at 515 nm. The internal and external quantum efficiencies (IQE/EQE) of YTU-G-1(SE) are close to unity, with values of 95.74 ± 0.5% and 88.67 ± 0.5%, respectively. Finally, we combined YTU-G-1(SE) with a commercial blue chip and a commercial red phosphor (Sr,Ca)AlSiN3:Eu2+ to fabricate a warm white light LED with a color temperature of 3736 K, a color-rendering index Ra of 88.2, and a lumen efficiency of 79.42 lm W-1. This work provides a new approach to regulating the emission of AIE and offers a novel idea for developing high-performance warm-white pc-WLEDs.

Construction of Porphyrin-Based Bimetallic Nanomaterials with Photocatalytic Properties.

The efficient synthesis of nanosheets containing two metal ions is currently a formidable challenge. Here, we attempted to dope lanthanide-based bimetals into porphyrin-based metal-organic skeleton materials (MOFs) by microwave-assisted heating. The results of the EDX, ICP, and XPS tests show that we have successfully synthesized porphyrin-based lanthanide bimetallic nanosheets (Tb-Eu-TCPP) using a household microwave oven. In addition, it is tested and experimentally evident that these nanosheets have a thinner thickness, a larger BET surface area, and higher photogenerated carrier separation efficiency than bulk porphyrin-based bimetallic materials, thus exhibiting enhanced photocatalytic activity and n-type semiconductor properties. Furthermore, the prepared Tb-Eu-TCPP nanomaterials are more efficient in generating single-linear state oxygen under visible light irradiation compared to pristine monometallic nanosheets due to the generation of bimetallic nodes. The significant increase in catalytic activity is attributed to the improved separation and transfer efficiency of photogenerated carriers. This study not only deepens our understanding of lanthanide bimetallic nanosheet materials but also introduces an innovative approach to improve the photocatalytic performance of MOFs.

Establishment and Clinical Application of the General Comfort Scale for Postoperative Lung Cancer Patients.

Background and purpose The concept of enhanced recovery after surgery (ERAS) not only reflects rapid perioperative recovery but also focuses on the comfort experience of inpatients. This study intends to establish a clinically applicable general comfort questionnaire (GCQ) for patients with lung cancer after surgery and verify its clinical application effect. Methods The comfort index items for postoperative lung cancer were formed by combining previous research and literature, clinically applied comfort scales, and expert interviews. The Delphi method was used to conduct two rounds of expert consultations to determine the final index and establish a postoperative comfort scale for lung cancer patients. This scale was used to conduct a questionnaire survey on 200 patients to test the reliability and validity of the scale. Results The comfort scale contains 3 dimensions and 10 items and is easy to operate and evaluate in clinical applications. The Cronbach's α coefficient of the comfort scale is 0.801, and the scale content validity index (SCVI/ave) is 0.97. The common factor 1 and 2 characteristic roots of scale structural validity evaluation are 3.257 and 1.352 respectively, both greater than 1, with cumulative variance contribution rates of 32.57% and 13.52%. Pain and getting out of bed are the main factors influencing patient comfort. Conclusion The postoperative comfort scale for lung cancer patients has high clinical application reliability and validity. This study identified pain and mobility (early ambulation or getting out of bed) as the primary factors influencing the postoperative comfort of lung cancer patients.

Multigene testing panels reveal pathogenic variants in sporadic breast cancer patients in northern China.

Background: Breast cancer, the most prevalent malignancy in women worldwide, presents diverse onset patterns and genetic backgrounds. This study aims to examine the genetic landscape and clinical implications of rare mutations in Chinese breast cancer patients. Methods: Clinical data from 253 patients, including sporadic and familial cases, were analyzed. Comprehensive genomic profiling was performed, categorizing identified rare variants according to the American College of Medical Genetics (ACMG) guidelines. In silico protein modeling was used to analyze potentially pathogenic variants' impact on protein structure and function. Results: We detected 421 rare variants across patients. The most frequently mutated genes were ALK (22.2%), BARD1 (15.6%), and BRCA2 (15.0%). ACMG classification identified 7% of patients harboring Pathogenic/Likely Pathogenic (P/LP) variants, with one case displaying a pathogenic BRCA1 mutation linked to triple-negative breast cancer (TNBC). Also identified were two pathogenic MUTYH variants, previously associated with colon cancer but increasingly implicated in breast cancer. Variants of uncertain significance (VUS) were identified in 112 patients, with PTEN c.C804A showing the highest frequency. The role of these variants in sporadic breast cancer oncogenesis was suggested. In-depth exploration of previously unreported variants led to the identification of three potential pathogenic variants: ATM c.C8573T, MSH3 c.A2723T, and CDKN1C c.C221T. Their predicted impact on protein structure and stability suggests a functional role in cancer development. Conclusion: This study reveals a comprehensive overview of the genetic variants landscape in Chinese breast cancer patients, highlighting the prevalence and potential implications of rare variants. We emphasize the value of comprehensive genomic profiling in breast cancer management and the necessity of continuous research into understanding the functional impacts of these variants.

Depression and risk of sarcopenia: a national cohort and Mendelian randomization study.

Background: Depression and the increased risk of sarcopenia are prevalent among the elderly population. However, the causal associations between these factors remain unclear. To investigate the potential association between depression and the risk of sarcopenia in older adults, this study was performed. Methods: In the baseline survey, a total of 14,258 individuals aged 40 and above from the China Health and Retirement Longitudinal Study (2015) participated. We initially described the baseline prevalence of the disease. Then, logistic regression and restricted cubic spline (RCS) regression were conducted to assess the relationship between depression and sarcopenia. Subgroup analysis was performed to validate the robustness of the findings. Additionally, we conducted Mendelian randomization analysis using the inverse variance weighting estimator to assess the causal relationship between depression and sarcopenia. Furthermore, we adopted six methods, including MR-Egger, simple median, weighted median, maximum likelihood, robust adjusted profile score (RAPS), and MR Pleiotropy Residual Sum and Outlier (MR-PRESSO), for sensitivity analyses. Results: Depression patients exhibited higher risks of sarcopenia in all five models adjusting for different covariates (P < 0.05). The RCS analysis demonstrated a linear relationship between depression and sarcopenia (P < 0.05). In the subgroup analysis, increased risk was observed among participants aged 60-70, married or cohabiting individuals, non-smokers, non-drinkers, those with less than 8 h of sleep, BMI below 24, and individuals with hypertension (all P < 0.05). Mendelian randomization results revealed that genetically proxied depression led to a reduction in appendicular skeletal muscle mass (all P < 0.05). Conclusion: Our study provides observational and causal evidences that depression can lead to sarcopenia. This finding emphasizes the importance of timely identification and management of depression, as well as implementing targeted educational programs as part of comprehensive strategies to prevent sarcopenia.

An Analysis of Public Perception and Concern Toward Electronic Cigarettes: Exploring Attitudes and Profiles.

Introduction The emergence of electronic cigarettes (e-cigarettes) poses a new challenge to tobacco control efforts. With their increasing popularity, particularly among youth, public concerns have been raised in Mainland China. Further investigation is necessary to fully understand the safety and potential adverse effects of e-cigarettes. Methods The Baidu search index (BSI) was employed using e-cigarette related terms from January 1, 2011, to April 4, 2022. The search volume for each term was recorded and analyzed for the search trend module, geodemographic module, search-demand module, regional preferences, demographic preferences, and user demand. Results According to our analysis, the total BSI for the 18 e-cigarette related search keywords was 39,027,819. The average annual percentage change of BSI indicated an upward trend for each of these categories, including health issues (p < 0.05), definition (p < 0.05), product and promotions (p < 0.05), and policy and regulations. Of all inquiries, 59.38% originated from females and 40.62% from males. The total valid BSI for e-cigarette related words was 165,076,588, and 11.59% of all search inquiries were from individuals aged 19 years and younger. Our analysis also revealed that the public's primary concerns regarding e-cigarettes were related to their quality and potential health issues. Conclusions E-cigarettes enjoy great popularity nationwide, but product quality and safety are major public concerns. Regulation of e-cigarettes for their standard production, quality control, advertisement, and target customers should be implemented promptly, and the public needs to have a clear perception of e-cigarettes, especially adolescents. E-cigarette related health damages or consequences require further investigation, and advertisements and promotions for e-cigarettes should be strictly controlled by the government.

17ß-Estradiol Mediates Staphylococcus aureus Adhesion in Vaginal Epithelial Cells via Estrogen Receptor α-Associated Signaling Pathway.

Staphylococcus aureus, a major opportunistic pathogen in aerobic vaginitis (AV), can potentially invade the host and occasionally cause infections. Estrogen is associated with an altered immune response of vaginal epithelial cells and prevention of certain vaginal infectious diseases. However, the molecular mechanisms involving estrogen and S. aureus adhesion to vaginal epithelial cells remain unclear. Thus, here, VK2/E6E7 vaginal epithelial cells were infected with S. aureus, and the role of the estrogen receptor α-associated signaling pathway (ERα/FAK/Src/iNOS axis) in S. aureus adhesion was evaluated. The estrogen-associated phosphorylation status of ERα, FAK, and Src and the protein level of iNOS were assessed by western blotting. We used a specific ERα inhibitor to validate the involvement of the ERα-associated signaling pathway. The results showed that with exposure to 1 nM estrogen for 24 h, transient ERα-associated pathway activation was observed, and the protein expression upregulation was accompanied by a dose-dependent increase in 17-ß-estradiol (E2) content and increased S. aureus adherence to vaginal epithelial cells. Estrogen-induced activation of the ERα/FAK/Src/iNOS axis was notably inhibited by the specific ERα inhibitor (ICI 182780). Simultaneously, a significant decrease in the number of adherent S. aureus was observed. However, this inhibitory effect diminished after inhibitor treatment for 24 h. Our findings suggested that the ERα-associated signaling pathway might be involved in S. aureus adherence to vaginal epithelial cells, which appeared to be linked to enhanced cell adhesion leading to AV.

Calix[4]arene-Derived 2D Covalent Organic Framework with an Electron Donor-Acceptor Structure: A Visible-Light-Driven Photocatalyst.

The calixarenes are ideal building blocks for constructing photocatalytic covalent organic frameworks (COFs), owing to their electron-rich and bowl-shaped π cavities that endow them with electron-donating and adsorption properties. However, the synthesis and structural confirmation of COFs based on calixarenes are still challenging due to their structural flexibility and conformational diversity. In this study, a calix[4]arene-derived 2D COF is synthesized using 5,11,17,23-tetrakis(p-formyl)-25,26,27,28-tetrahydroxycalix[4]arene (CHO-C4A) as the electron donor and 4,7-bis(4-aminophenyl)-2,1,3-benzothiadiazole (BTD) as the acceptor. The powder X-ray diffraction data and theoretical simulation of crystal structure indicate that COF-C4A-BTD exhibits high crystallinity and features a non-interpenetrating undulating 2D layered structure with AA-stacking. The density functional theory theoretical calculation, transient-state photocurrent tests, and electrochemical impedance spectroscopy confirm the intramolecular charge transfer behavior of COF-C4A-BTD with a donor-acceptor structure, leading to its superior visible-light-driven photocatalytic activity. COF-C4A-BTD exhibits a narrow band gap of 1.99 eV and a conduction band energy of -0.37 V versus normal hydrogen electrode. The appropriate energy band structure can facilitate the participation of ·O2- and h+ . COF-C4A-BTD demonstrates high efficacy in removing organic pollutants, such as bisphenol A, rhodamine B, and methylene blue, with removal rates of 66%, 85%, and 99% respectively.

Near-Unity Energy Transfer from Uranyl to Europium in a Heterobimetallic Organic Framework with Record-Breaking Quantum Yield.

Lanthanide organic frameworks (Ln-MOFs) have attracted increasing research enthusiasm as photoluminescent materials. However, limited luminescence efficiency stemming from restricted energy transfer efficiency from the organic linker to the metal center hinders their applications. Herein, a uranyl sensitization approach was proposed to boost the luminescence efficiency of Ln-MOFs in a distinct heterobimetallic uranyl-europium organic framework. The record-breaking photoluminescence quantum yield (PLQY, 92.68%) among all reported Eu-MOFs was determined to benefit from nearly 100% energy transfer efficiency between UO22+ and Eu3+. Time-dependent density functional theory and ab initio wave-function theory calculations confirmed the overlap of excited state levels between UO22+ and Eu3+, which is responsible for the efficient energy transfer process. Coupled with intrinsically strong stopping power toward X-ray of the uranium center, SCU-UEu-2 features an ultralow detection limit of 1.243 µGyair/s, outperforming the commercial scintillator LYSO (13.257 µGyair/s) and satisfying the requirement of X-ray diagnosis (below 5.5 µGyair/s) in full.

Differences of genomic alterations and heavy metals in non-small cell lung cancer with different histological subtypes.

PURPOSE: This study aimed to explore the correlations among heavy metals concentration, histologic subtypes and molecular characteristics in patients with non-small cell lung cancer (NSCLC). METHODS: In this study, an NGS panel of 82 tumor-associated genes was used to identify genomic alternations in 180 newly diagnosed patients with NSCLC. The concentrations of 18 heavy metals in the serum samples were detected by inductively coupled plasma emission spectrometry (ICP-MS). RESULTS: A total of 243 somatic mutations of 25 mutant genes were identified in 115 of 148 patients with LUAD and 45 somatic mutations of 15 mutant genes were found in 24 of 32 patients with LUSC. The genomic alternations, somatic interactions, traditional serum biomarkers, and heavy metals were markedly different between patients with LUAD and LUSC. Moreover, patients with LUSC were significantly positively correlated with Ba, but not LUAD. Lastly, patients with EGFR mutations presented significant negative correlations with Cd and Sr, whereas patients with TP53 mutations showed a significant positive correlation with Pb. CONCLUSION: The genomic alternations, somatic interactions, traditional serum biomarkers, and heavy metals were different between patients with LUAC and LUSC, and heavy metals (e.g., Ba, Pb, and Cd) may contribute to the tumorigenesis of NSCLC with different histological and molecular subtypes.

Fabrication of a Large-Area Flexible Scintillating Membrane for High-Resolution X-ray Imaging Using an AIEgen-Functionalized Metal-Organic Framework.

With the growing demand for X-ray imaging, especially for three-dimensional objects with curved surfaces, a large-area flexible X-ray imaging membrane based on scintillating materials becomes the focus of vigorous investigation. Among the developed scintillators, metal-organic frameworks (MOFs) featuring tunable photophysical properties and marked luminescence stability hold great promise for serving as ideal X-ray scintillators. Here, we report a flexible composite scintillating membrane with superior imaging performance. The membrane is achieved by embedding an aggregation-induced emission (AIE) luminogen (AIEgen, H4ETTC)-functionalized MOF scintillator (Y-PCN-94) into a polymer matrix (PDMS). Notably, Y-PCN-94 exhibits a strong AIE effect under both ultraviolet (UV) light and X-ray irradiation, which is also the first time that the AIE effect was observed in the MOF system under an ionizing radiation field. This also gives the material promising radioluminescence properties, such as a low X-ray detection limit (1.6 µGy s-1) and high imaging resolution (>14.3 lp mm-1), which can be mainly attributed to the combination of the AIE effect and strong X-ray stopping power. This work demonstrates that incorporating AIEgens into MOFs or other frameworks can offer an alternative approach for producing high-performance X-ray scintillators.

Deep regression using 99mTc-DTPA dynamic renal imaging for automatic calculation of the glomerular filtration rate.

OBJECTIVES: To develop and evaluate an artificial intelligence (AI) system that can automatically calculate the glomerular filtration rate (GFR) from dynamic renal imaging without manually delineating the regions of interest (ROIs) of kidneys and the corresponding background. METHODS: This study was a single-center retrospective analysis of the data of 14,634 patients who underwent 99mTc-DTPA dynamic renal imaging. Two systems based on convolutional neural networks (CNN) were developed and evaluated: sGFRa predicts the radioactive counts of ROIs and calculates GFR using the Gates equation and sGFRb directly predicts GFR from dynamic renal imaging without using other information. The root-mean-square error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and R2 were used to evaluate the performance of our approach. RESULTS: sGFRa achieved an RMSE of 5.05, MAE of 4.03, MAPE of 6.07%, and R2 of 0.93 for total GFR while sGFRb achieved an RMSE of 7.61, MAE of 5.92, MAPE of 8.92%, and R2 of 0.85 for total GFR. The accuracy of sGFRa and sGFRb in determining the stage of chronic kidney disease was 87.41% and 82.44%, respectively. CONCLUSIONS: The findings of sGFRa show that automatic GFR calculation based on CNN and using dynamic renal imaging is feasible and efficient and, additionally, can aid clinical diagnosis. Furthermore, the promising results of sGFRb demonstrate that CNN can predict GFR from dynamic renal imaging without additional information. KEY POINTS: • Our CNN-based AI systems can automatically calculate GFR from dynamic renal imaging without manually delineating the ROIs of kidneys and the corresponding background. • sGFRa accurately predicted the radioactive counts of ROIs and calculated GFR using the Gates method. • sGFRb-predicted GFR directly without any parameters related to the Gates equation.

Registered Clinical Trials for Artificial Intelligence in Lung Disease: A Scoping Review on ClinicalTrials.gov.

Clinical trials are the most effective tools to evaluate the advantages of various diagnostic and treatment modalities. AI used in medical issues, including screening, diagnosis, and treatment decisions, improves health outcomes and patient experiences. This study's objective was to investigate the traits of registered trials on artificial intelligence for lung disease. Clinical studies on AI for lung disease that were present in the ClinicalTrials.gov database were searched, and fifty-three registered trials were included. Forty-six (72.1%) were observational trials, compared to seven (27.9%) that were interventional trials. Only eight trials (15.4%) were completed. Thirty (56.6%) trials were accepting applicants. Clinical studies often included a large number of cases; for example, 24 (32.0%) trials included samples of 100-1000 cases, while 14 (17.5%) trials included samples of 1000-2000 cases. Of the interventional trials, twenty (15.7%) were retrospective studies and twenty (65.7%) were prospective studies.

Differences in actionable genomic alterations between brain metastases and non­brain metastases in patients with non­small cell lung cancer.

Brain metastases (BM) have been closely associated with increased morbidity and poor survival outcomes in patients with non­small cell lung cancer (NSCLC). Excluding risk factors in histological subtypes, genomic alterations, including epidermal growth factor receptor mutations and anaplastic lymphoma kinase (ALK) rearrangements have been also regarded as greater risk factors for BM in the aspect of molecular subtypes. In the present study, 69 tumor tissues and 51 peripheral blood samples from patients with NSCLC were analyzed using a hybridization capture­based next­generation sequencing (NGS) panel, including 95 known cancer genes. Among the 90 patients with stage IV NSCLC, 26 cases suffered from BM and 64 cases did not. In total, 174 somatic mutations in 35 mutated genes were identified, and 12 of these genes were concurrently present in the BM group and the non­BM group. Importantly, five mutated genes including ALK, cytidine deaminase (CDA), SMAD family member 4 (SMAD4), superoxide dismutase 2 (SOD2) and Von Hippel­Lindau tumor suppressor (VHL) genes were uniquely detected in the BM group, and they were enriched in the Hippo signaling pathway, pyrimidine metabolism and pantothenate and co­enzyme A (CoA) biosynthesis, as demonstrated using Kyoto Encyclopedia of Genes and Genomes enrichment analysis. RNA polymerase II transcription regulator complex and promyelocytic leukemia nuclear body were the top functional categories according to the Gene Ontology enrichment analysis in the BM group and non­BM group, respectively. Furthermore, 43.33% (13/30) of mutated genes were detected by both tumor tissue deoxyribonucleic acid (DNA) and plasma­derived circulating tumor DNA (ctDNA) in the non­BM group, while this percentage was only limited to 29.41% (5/17) in the BM group. To summarize, significant differences in somatic mutations, somatic interactions, key signaling pathways, functional biological information, and clinical actionability for the therapy of targeted agents were founded between the BM group and the non­BM group, and ctDNA analysis may by applied as a more credible alternative for genomic profiling in patients with advanced NSCLC without BM, due to its higher consistency for genomic profiling between ctDNA analysis and tissue DNA analysis.